Phase 3 Efficacy and Safety Study of BG00012 in Pediatric Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)

NCT02283853 | Completed Phase 3 DMC

• 2 other identifiers: 109MS3062013-002318-11
• Study Type: interventional
• Target: 156
• Locations: 17 countries
• Sites: 59

Brief Summary

The main objectives of Part 1 are as follows: To evaluate the safety, tolerability, and efficacy of BG00012 in pediatric subjects with RRMS, as compared with a disease-modifying treatment and to assess health outcomes and evolution of disability. The primary objective of Part 2 is to evaluate the long-term safety of BG00012 in subjects who completed Week 96 in Part 1 of Study 109MS306. The secondary objective of Part 2 is to describe the long-term MS outcomes of BG00012 in subjects who completed Week 96 in Part 1 of Study 109MS306.

Conditions

Relapsing-Remitting Multiple Sclerosis

Keywords

Pediatrics

Outcome Measures

Primary Outcomes (3)

• Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans

  Part 1

  At week 96

• Number of Participants That Experience Adverse Events (AEs) or Serious Adverse Events (SAEs)

  Part 2 will be an optional open-label extension phase in subjects who complete Part 1 and who meet the Part 2 entry criteria.

  Up to 7 years

• Number of Participants Who Discontinue Study Treatment due to an AE

  Part 2

  Up to 7 years

Secondary Outcomes (23)

• The Number of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans

  At Week 24 and Week 96

• Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans

  At Week 24 and Week 48

• Proportion of Participants Free of New MRI Activity as measured by Brain MRI Scans

  At Weeks 24, 48 and 96

• Time to First Relapse

  Up to Week 96

• Proportion of Participants Who Do Not Experience Relapse

  Up to Week 96

Study Arms (2)

BG00012

EXPERIMENTAL

Participants will receive the recommended dose of 240 mg orally, twice a day

Drug: dimethyl fumarate

IFN β-1a (Avonex)

ACTIVE COMPARATOR

Participants will receive the recommended dose of 30 μg (weekly)

Drug: Interferon β-1a

Interventions

dimethyl fumarate DRUG

administered orally

Also known as: BG00012, Tecfidera

BG00012

Interferon β-1a DRUG

administered by intramuscular injection

Also known as: Avonex

IFN β-1a (Avonex)

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Must have a body weight of ≥30 kg.
• Must have a diagnosis of RRMS (consensus definition for pediatric RRMS \[Krupp 2007\]).
• Must be ambulatory with a baseline EDSS score between 0 and 5.5, inclusive.
• Must have experienced at least 1 of the following 3 conditions: a) at least 1 relapse within the last 12 months prior to Day 1 with a prior brain MRI demonstrating lesions consistent with MS; b) at least 2 relapses within the last 24 months prior to Day 1, with a prior brain MRI demonstrating lesions consistent with MS; c) evidence of Gd-enhancing lesions of the brain on an MRI performed within the 6 weeks prior to Day 1.
• Must be neurologically stable, with no evidence of relapse within 50 days prior to Day 1 and no evidence of corticosteroid treatment within 30 days prior to Day 1.
• Subjects of childbearing potential who are sexually active must be willing to practice effective contraception during the study and be willing and able to continue contraception for at least 30 days after their final dose of study treatment.

You may not qualify if:

• Primary progressive, secondary progressive, or progressive relapsing MS (as defined by \[Lublin and Reingold 1996\]). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Subjects with these conditions may also have superimposed relapses but are distinguished from relapsing-remitting subjects by the lack of clinically stable periods or clinical improvement.
• Disorders mimicking MS, such as other demyelinating disorders (e.g., acute disseminated encephalomyelitis), systemic autoimmune disorders (e.g., Sjögren disease, lupus erythematosus), metabolic disorders (e.g., dystrophies), and infectious disorders.
• History of premalignant or malignant disease. Subjects with basal cell carcinoma that has been completely excised prior to screening will remain eligible.
• History of severe allergic or anaphylactic reactions, or known drug hypersensitivity to DMF, fumaric acid esters, or interferon beta-1a (IFN Beta-1a).
• History of abnormal laboratory results indicative of any significant endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, renal, and/or any other major disease that would preclude participation in a clinical study.
• History of clinically significant cardiovascular, pulmonary, GI, dermatologic, growth, developmental, psychiatric (including depression), neurologic (other than MS), and/or other major disease that would preclude participation in a clinical study.
• History of human immunodeficiency virus.
• An MS relapse that has occurred within 50 days prior to Day 1 AND/OR the subject has not stabilized from a previous relapse prior to Day 1.
• Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment.
• For the PD/PK subset of subjects: subjects unable to swallow the BG00012 capsule whole.
• Key Treatment history
• Any previous treatment with Fumaderm (fumaric acid esters) or BG00012.
• Prior treatment with any of the following: total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination, any therapeutic monoclonal antibody, with the exception of rituximab or natalizumab.
• Prior treatment with any of the following medications within the 12 months prior to Day 1: mitoxantrone, cyclophosphamide, rituximab.
• Prior treatment with any of the following medications or procedures within 6 months prior to Day 1: fingolimod; teriflunomide; natalizumab; cyclosporine; azathioprine; methotrexate; mycophenolate mofetil; laquinimod; intravenous (IV) immunoglobulin; plasmapheresis or cytapheresis

Sponsors & Collaborators

• Biogen: lead

Study Sites (62)

Boston Children's Hospital

Boston, Massachusetts, 2115, United States

Location

The Rector and Visitors of the University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Universitair Kinderziekenhuis Koningin Fabiola

Brussels, 1020, Belgium

Location

Universitair Ziekenhuis Ghent

Ghent, 9000, Belgium

Location

MHATNP 'Sv.Naum', EAD

Sofia, 1113, Bulgaria

Location

University of Calgary - Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 656 91, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Nemocnice Jihlava p.o.

Jihlava, 58633, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Århus Universitetshospital

Aarhus N, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense Universitetshospital

Odense, 5000, Denmark

Location

CHU Strasbourg - Hôpital Hautepierre

Strasbourg, Bas Rhin, 67098, France

Location

Hôpital de la Timone

Marseille, Bouches-du-Rhône, 13385, France

Location

CHU Dijon -BOCAGE CENTRAL

Dijon, Côte-d'Or, 21079, France

Location

Hopital Gui de Chauliac

Montpellier, Herault, 34295, France

Location

CHU Rennes - Hopital Pontchaillou

Rennes, Ille Et Vilaine, 35033, France

Location

Hôpital de Brabois Enfants

Vandœuvre-lès-Nancy, Meurthe Et Moselle, 54500, France

Location

Hopital Roger Salengro - CHU Lille

Lille, Nord, 59037, France

Location

CHU Clermont Ferrand - Hôpital d'Estaing

Clermont-Ferrand, Puy De Dome, 63003, France

Location

Hopital Neurologique Pierre Wertheimer

Bron, Rhone, 69677, France

Location

CHU Amiens - Hopital Sud

Amiens, Somme, 80054, France

Location

Hôpital Bicêtre

Le Kremlin-Bicêtre, Val De Marne, 94275, France

Location

Universitaetsklinikum Augsburg

Augsburg, Bavaria, 86156, Germany

Location

Klinikum der Universitaet Muenchen

Munich, Bavaria, 80337, Germany

Location

Katholisches Klinikum Bochum gGmbH

Bochum, North Rhine-Westphalia, 44791, Germany

Location

Semmelweis Egyetem

Budapest, 1083, Hungary

Location

Heim Pal Orszagos Gyermekgyogyaszati Intezet

Budapest, 1089, Hungary

Location

Hadassah University Hospital - Ein Kerem

Jerusalem, 91120, Israel

Location

Schneider Children's Medical Center

Petah Tikva, 4920235, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

Location

Azienda Socio Sanitaria Territoriale della Valle Olona (presidio di Gallarate)

Gallarate, Varese, 21013, Italy

Location

Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari

Bari, 70124, Italy

Location

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliera Universitaria 'Federico II'

Napoli, 80131, Italy

Location

Azienda Ospedale-Università di Padova

Padua, 35128, Italy

Location

Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone

Palermo, 90127, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, 00165, Italy

Location

Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza

Roma, 00189, Italy

Location

Ibn Sina Hospital

Ash Shuwaykh, 12345, Kuwait

Location

SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa

Bialystok, 15-274, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-211, Poland

Location

Instytut Centrum Zdrowia Matki Polki

Lodz, 93-338, Poland

Location

Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu

Poznan, 60-355, Poland

Location

Instytut 'Pomnik - Centrum Zdrowia Dziecka'

Warsaw, 04-730, Poland

Location

Clinic of Neurology and Psychiatry for Children and Youth

Belgrade, 11000, Serbia

Location

Mother and Child Health Care Institute of Serbia ,,Dr Vukan Cupic''

Belgrade, 11000, Serbia

Location

University Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat, Barcelona, 8950, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Córdoba, 14011, Spain

Location

Hospital Universitario de Torrejon

Torrejón de Ardoz, Madrid, 28850, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Sahlgrenska Sjukhuset

Gothenburg, 41345, Sweden

Location

Karolinska

Stockholm, SE-113 61, Sweden

Location

Hacettepe University Medical Faculty

Ankara, 06100, Turkey (Türkiye)

Location

Akdeniz University Faculty of Medicine

Antalya, 07070, Turkey (Türkiye)

Location

Evelina London Children's Hospital

London, Greater London, SE1 7EH, United Kingdom

Location

The National Hospital for Neurology & Neurosurgery

London, Greater London, WC1N 3BG, United Kingdom

Location

Great Ormond Street Hospital for Children

London, Greater London, WC1N 3JH, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

Related Publications (1)

• Vermersch P, Scaramozza M, Levin S, Alroughani R, Deiva K, Pozzilli C, Lyons J, Mokliatchouk O, Pultz J, N'Dure F, Liu S, Badwan R, Branco F, Hood-Humphrey V, Franchimont N, Hanna J, Maghzi AH. Effect of Dimethyl Fumarate vs Interferon beta-1a in Patients With Pediatric-Onset Multiple Sclerosis: The CONNECT Randomized Clinical Trial. JAMA Netw Open. 2022 Sep 1;5(9):e2230439. doi: 10.1001/jamanetworkopen.2022.30439.

  PMID: 36169959 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Dimethyl Fumarate; Interferon beta-1a

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2014
• First Posted: November 5, 2014
• Study Start: August 28, 2014
• Primary Completion: July 8, 2025
• Study Completion: July 8, 2025
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

DE (3); SE (2); IT (9); BU (1); KU (1); US (2); CA (1); IL (3); BE (2); HU (2); ES (4); FR (11); DK (3); PL (5); GB (4); TU (2); CZ (4)